PROJECT SUMMARY Acute compartment syndrome (ACS) remains one of the most devastating and often overlooked traumatic musculoskeletal disorders in clinical practice. In this condition, pressure increases in one of the body?s space- limited compartments, due most commonly to direct trauma or bone fracture, resulting ultimately in an ischemic injury to all of the compartment?s contents, including muscle and nerve. Once a full-blown compartment syndrome develops, the consequences are uniformly catastrophic, with permanent muscle and nerve loss, sometimes necessitating amputation of the entirely non-functional limb. If caught before irrevocable damage is done, aggressive surgical decompression, via fasciotomy, can be performed to relieve the pressure in the compartment and allowing the muscles and nerves to recover. However, current approaches for assessing the development of ACS, outside of the physical examination, are limited. The standard method involves the insertion of a pressure monitor. There are no effective approaches for the continuous surveillance for the development of ACS after an injury. One technology that may be especially sensitive to the development of ACS is that of electrical impedance myography (EIM). In EIM, a weak, high-frequency electrical current is passed between a number of electrodes overlying a muscle or muscle group of interest and the resulting surface voltages measured by a second set of electrodes. The health status of the underlying muscle impacts the measured voltages in consistent and predictable fashion. For instance, increasing myofiber edema and injury would be expected to lead to reductions in the impedance resistance measure. The development of EIM for medical and broader health use is the underlying focus of Myolex, Inc, a small business concern based in San Francisco and Boston. To date, the technology has been shown to be effective in a wide variety of disorders that impact the muscle either directly or indirectly, including muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia (muscle wasting in the elderly). Additional work has also suggested that EIM is sensitive to primary muscle injury. In this study we propose to extend this work, seeking to develop EIM as a non-invasive, convenient monitoring tool to assess the development of ACS. This will allow health care professionals to monitor compartments for ACS after predisposing injury intervene and to intervene at a sufficiently early point, so as to avoid permanent injury. In our first specific aim, we will use a rat ACS model to assess changes in EIM values and the corresponding alterations in pathology at several severities of injury to establish a time course of change and the relationship to impedance values. In Specific Aim 2, using tissue data obtained in Aim 1 and anatomic models, we will design electrode arrays that will be most effective at detecting the development of ACS in a porcine model and in human subjects for use in our planned Phase 2 studies.